Variant 1-41511257-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_024503.5(HIVEP3):c.6415G>A(p.Glu2139Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,602,634 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 5 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.612

Variant links:

Genes affected

HIVEP3 (HGNC:13561): (HIVEP zinc finger 3) This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Sep 2011]

HIVEP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003950864).

BP6

Variant 1-41511257-C-T is Benign according to our data. Variant chr1-41511257-C-T is described in ClinVar as [Benign]. Clinvar id is 3035562.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.6415G>A	p.Glu2139Lys	missense_variant	9/9	ENST00000372583.6
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6412G>A	p.Glu2138Lys	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6 linkuse as main transcript	c.6415G>A	p.Glu2139Lys	missense_variant	9/9	1	NM_024503.5	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6412G>A	p.Glu2138Lys	missense_variant	8/8	1		A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6412G>A	p.Glu2138Lys	missense_variant	8/8			A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1342G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00741

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000678

AC:

162

AN:

238854

Hom.:

AF XY:

0.000488

AC XY:

AN XY:

129112

show subpopulations

Gnomad AFR exome

AF:

0.00836

Gnomad AMR exome

AF:

0.000384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000279

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000465

Gnomad OTH exome

AF:

0.000512

GnomAD4 exome

AF:

0.000253

AC:

367

AN:

1450402

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

137

AN XY:

719958

show subpopulations

Gnomad4 AFR exome

AF:

0.00777

Gnomad4 AMR exome

AF:

0.000521

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000200

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000995

Gnomad4 OTH exome

AF:

0.000835

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152232

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00739

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000411

Hom.:

Bravo

AF:

0.00272

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00682

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000759

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HIVEP3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.84

.;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.83

.;N;N

REVEL

Benign

0.051

Sift

Benign

0.032

.;D;D

Sift4G

Benign

0.090

.;T;T

Polyphen

0.64

P;P;P

Vest4

0.090, 0.13

MVP

0.28

MPC

0.25

ClinPred

0.015

GERP RS

3.7

Varity_R

0.14

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over